International Immunology, Vol. 12, No. 10, 1417-1423,
October 2000
© 2000 Japanese Society for Immunology
Negative regulation of B cell receptor-mediated signaling in B-1 cells through CD5 and Ly49 co-receptors via Lyn kinase activity
Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
Correspondence to: T. Watanabe
CD5+ B-1 cells are known to be unresponsive to B cell receptor (BCR)-mediated growth signals but instead undergo apoptosis. However, the B-1 cells from Lyn kinase-deficient (Lyn–/–) mice exhibited an enhanced proliferative response upon BCR cross-linking. It has been reported that BCR-mediated signaling in B-1 cells is negatively regulated by signals from CD22, CD5 and CD72 co-receptors, and that Lyn kinase plays a crucial role in tyrosine phosphorylation of immunoreceptor tyrosine-based inhibitory motifs on the CD22 and CD72, which recruits SHP-1 to the BCR complex. We found that Lyn kinase is also essential for the tyrosine phosphorylation of CD5 and subsequent recruitment of SHP-1 in B-1 cells upon cross-linking of BCR. Moreover, a distinct subpopulation of B-1 cells was found to express cell surface Ly49, which is known as a MHC class I-binding negative regulatory receptor on NK cells. Ly49 was rapidly tyrosine phosphorylated upon cross-linking of BCR and SHP-1 was found to recruit to the phosphorylated Ly49. Addition of F(ab')2 fragments of anti-Ly49 antibodies partially blocked negative signals in B-1 cells. Thus two co-receptors, CD5 and Ly49, which are unique to B-1 cells, play a role in the regulation of B-1 cell activation. These results indicate that BCR-mediated signals in B-1 cells are strictly and negatively regulated through multiple pathways, that are dependent on Lyn kinase activity.
Keywords: autoimmunity, hyper-proliferation, immunoreceptor tyrosine-based inhibitory motif, phosphatase
Transmitting editor: M. Taniguchi
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